The proposed research will extend previous observations indicating that immune processes are subject to behavioral conditioning. Using an illness-induced taste aversion paradigm, rats and/or mice are conditioned by pairing a distinctively flavored drinking solution (the conditioned stimulus) with an immunosuppressive agent (e.g., cyclophosphamide, methotrexate), the unconditioned stimulus. After conditioning, all animals will be injected with antigen (e.g., SRBC, TNP-LPS). Antibody titers are measured after antigen administration in conditiond animals that are again exposed to the conditioned stimulus or that receive no further experimental treatment, and in nonconditioned and placebo-treated groups. In addition to assessing immunosuppression (and immuno-enhancement) associated with thymus dependent and thymus independent humoral responses, the effects of conditioning on cell-mediated responses (host-vs.-graft reaction, delayed hypersensitivity) will be studied. The biological significance of conditioned immunosuppression will also be assessed by measuring the immune responses and ultimate survival of rats to experimental allergic encephalomyelitis and a spontaneously developing autoimmune disease in NZBxNZW mice which is an experimental model of systemic lupus erythematosus in humans - both of which are sensitive to the effects of immunosuppressive chemotherapy.